HDV RNA Positivity Linked to Greater Risk of Severe Liver-Related Outcomes

Patients with chronic hepatitis D virus (HDV) infection are at an increased risk of severe liver-related outcomes, including liver decompensation, hepatocellular carcinoma (HCC), liver transplantation, and death, according to findings from a recent study.1

The multicenter, retrospective, real-world cohort study included patients from 8 Belgian hospitals with clinical follow-up spanning over 2 decades and found HDV RNA-positive patients were more frequently diagnosed with advanced liver fibrosis at baseline and had a 4.7-fold higher risk of severe liver-related outcomes than those with undetectable HDV RNA viremia.1

Known as a "satellite virus", HDV affects nearly 5% of people globally who have a chronic infection with hepatitis B virus (HBV). HDV-HBV co-infection is considered the most severe form of chronic viral hepatitis due to more rapid progression to HCC and liver-related death.2,3

“It is clear that uniform HDV diagnostic assays combined with long-term, large cohort studies are required to better characterize the natural history of HBV-HDV coinfections and determine the risk factors that define the disease progression and severity,” Thomas Vanwolleghem, MD, PhD, a professor of hepatology at the University of Antwerp, and colleagues wrote.1

To investigate the long-term outcomes of chronic HDV and identify risk factors for severe liver-related outcomes, investigators conducted a retrospective cohort study of HBV-HDV coinfected patients identified at the National Reference Centre for Viral Hepatitis, which performs confirmatory HDV testing for most of the hospitals and laboratories throughout Belgium. The study enrolled patients who were HBsAg or HBV DNA positive; anti-HDV or HDV RNA positive; and had ≥ 1 follow-up visit.1

Severe liver-related outcomes were defined as HCC, liver transplantation, death, or liver decompensation according to their clinical presentation with ascites, hepatic encephalopathy, or variceal bleeding and were recorded during a median 6.2 (interquartile range [IQR] 3.3–10.2) years of follow-up.1

After excluding repeat patients seen at several hospitals and those with insufficient baseline data, a total of 162 individual patients were included in the study. The median age at baseline was 36.4 (IQR, 28.8–43.8) years. Patients were predominantly male (63.0%) and of European or African origin (42.6% and 39.5%, respectively).1

At baseline, 68 (44.7%) patients were diagnosed with advanced liver fibrosis. Of 143 patients with ≥ 1 HDV RNA result, 64.3% were HDV RNA positive at the last evaluation. Investigators noted patients with detectable HDV RNA were more frequently diagnosed with advanced liver fibrosis at baseline compared to those with undetectable HDV RNA (51.1% vs 27.1%; P = .007).1

During follow-up, 40 (24.7%) patients had ≥ 1 severe liver-related outcome. In total, 35 patients developed ≥ 1 episode of liver decompensation, 16 patients were diagnosed with HCC, 15 patients underwent liver transplantation, and 9 deaths were recorded, resulting in a 5- and 10-year cumulative severe liver outcome probability of 22.0% and 31.0%, respectively.1

Investigators noted 82.5% of the patients with a severe liver-related outcome had ≥ 1 HDV RNA result available. Of those patients, 87.9% were HDV RNA positive at the last evaluation.1

Upon analysis, patients with a positive HDV RNA had a higher chance of developing any severe liver-related outcome compared to those with a negative result (P = .001), including higher risks for liver decompensation (P = .002), HCC (P = .003), and need for liver transplantation (P = .027). However, there was no significant difference in overall survival between the groups (P = .21).1

Multivariate analyses identified HDV RNA positivity as well as several markers for liver disease severity, including International Normalised Ratio, platelet count, and advanced fibrosis at baseline, and age at admission as independent risk factors for severe liver-related outcomes.1

This multicentric retrospective real-world cohort study, including 162 patients from 8 Belgian hospitals with clinical follow-up spanning over two decades, shows that severe liver-related outcomes, including liver decompensation, HCC, liver transplantation, and death, are frequent in patients with a chronic hepatitis delta infection,” investigators concluded.1 “HDV RNA-positive patients were more frequently diagnosed with advanced liver fibrosis at baseline and have a 4.7-fold higher risk for severe liver-related outcomes than those with undetectable HDV RNA viremia.”

References

1. Furquim d'Almeida A, Ho E, Govaerts L, et al. Severe Liver-Related Outcomes in Patients With Hepatitis Delta: Results From a Multi-Ethnic Multicenter Long-Term Follow-Up Study. J Viral Hepat. doi:10.1111/jvh.14060

2. US Centers for Disease Control and Prevention. Hepatitis D Basics. Accessed February 18, 2025. https://www.cdc.gov/hepatitis-d/about/index.html

3. World Health Organization. Hepatitis D. July 20, 2023. Accessed February 18, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d